Induction of a long noncoding rn A Transcript, NR-045064, promotes defense gene transcription and facilitates intestinal epithelial cell responses against cryptosporidium infection

Min Li, Ai Yu Gong, Xin Tian Zhang, Yang Wang, Nicholas W. Mathy, Gislaine A. Martins, Juliane K. Strauss-Soukup, Xian-Ming Chen

Research output: Contribution to journalArticle

Abstract

Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding rn A (lncrn A) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncrn A genes, including NR045064, in infected cells is controlled by the NF-kB signaling. Functionally, inhibition of NR045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncrn As, such as NR045064, play a role in regulating epithelial defense against microbial infection. The Journ Al of Immunology, 2018, 201: 3630-3640.

Original languageEnglish (US)
Pages (from-to)3630-3640
Number of pages11
JournalJournal of Immunology
Volume201
Issue number12
DOIs
StatePublished - Dec 15 2018

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Cryptosporidium
Epithelial Cells
Infection
Genes
Histone Code
vif Genes
Chromatin Assembly and Disassembly
NF-kappa B
Oligodeoxyribonucleotides
Intestinal Mucosa
Allergy and Immunology
Inbred C57BL Mouse
Epigenomics
Developing Countries
Diarrhea
Parasites

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Induction of a long noncoding rn A Transcript, NR-045064, promotes defense gene transcription and facilitates intestinal epithelial cell responses against cryptosporidium infection. / Li, Min; Gong, Ai Yu; Zhang, Xin Tian; Wang, Yang; Mathy, Nicholas W.; Martins, Gislaine A.; Strauss-Soukup, Juliane K.; Chen, Xian-Ming.

In: Journal of Immunology, Vol. 201, No. 12, 15.12.2018, p. 3630-3640.

Research output: Contribution to journalArticle

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abstract = "Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding rn A (lncrn A) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncrn A genes, including NR045064, in infected cells is controlled by the NF-kB signaling. Functionally, inhibition of NR045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncrn As, such as NR045064, play a role in regulating epithelial defense against microbial infection. The Journ Al of Immunology, 2018, 201: 3630-3640.",
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